Evidence map›Paper›PMID 34963894›Full record

ArticleACS central science2021

A Highly Sensitive Fluorescent Akt Biosensor Reveals Lysosome-Selective Regulation of Lipid Second Messengers and Kinase Activity.

Mingyuan Chen, Tengqian Sun, Yanghao Zhong, Xin Zhou, Jin Zhang

Open access · diamondAbstract read
In one paragraph

Article in ACS central science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 36 citations in OpenAlex.

  1. PI(3,5)PScience advances · 2026
    Article
  2. Review
  3. A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Two novel red-FRET ERK bosensors in the 670-720 nm range.Journal of biological engineering · 2025
    Article
  8. Review
  9. Article
  10. Lysosomal PIPProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Mingyuan ChenDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
Tengqian SunDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
Yanghao ZhongDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
Xin ZhouDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.ORCID https://orcid.org/0000-0001-7145-7823
University of California San Diego · US

Funding

Signal Transduction by PI3K/mTORR01DE030497 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUTKIND, JORGE SILVIO, ZHANG, JIN · 2021 to 2025
$2.4M
NIDCR NIH HHS R01 DE030497
6 · The paper itself

Abstract

The serine/threonine protein kinase Akt regulates a wide range of cellular functions via phosphorylation of various substrates distributed throughout the cell, including at the plasma membrane and endomembrane compartments. Disruption of compartmentalized Akt signaling underlies the pathology of many diseases such as cancer and diabetes. However, the specific spatial organization of Akt activity and the underlying regulatory mechanisms, particularly the mechanism controlling its activity at the lysosome, are not clearly understood. We developed a highly sensitive excitation-ratiometric Akt activity reporter (ExRai-AktAR2), enabling the capture of minute changes in Akt activity dynamics at subcellular compartments. In conjunction with super-resolution expansion microscopy, we found that growth factor stimulation leads to increased colocalization of Akt with lysosomes and accumulation of lysosomal Akt activity. We further showed that 3-phosphoinositides (3-PIs) accumulate on the lysosomal surface, in a manner dependent on dynamin-mediated endocytosis. Importantly, lysosomal 3-PIs are needed for growth-factor-induced activities of Akt and mechanistic target of rapamycin complex 1 (mTORC1) on the lysosomal surface, as targeted depletion of 3-PIs has detrimental effects. Thus, 3-PIs, a class of critical lipid second messengers that are typically found in the plasma membrane, unexpectedly accumulate on the lysosomal membrane in response to growth factor stimulation, to direct the multifaceted kinase Akt to organize lysosome-specific signaling.

Identifiers

PMID34963894
PMCPMC8704034
OpenAlexW4200584233

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.